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CCR2-dependent CX3CR1+ colonic macrophages promote Enterococcus faecalis dissemination

Kevin C Jennings1,2, Kaitlin E Johnson1,2, Michael A Hayward1,3

  • 1Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Infection and Immunity
|April 17, 2024
PubMed

Insights

Colonic macrophages facilitate Enterococcus faecalis infections by aiding bacterial spread to lymph nodes. Targeting macrophage migration may offer new strategies against these opportunistic pathogens.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Enterococci are common gut bacteria and a leading cause of hospital-acquired infections.
  • Understanding how these bacteria spread within the host is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of colonic macrophages in Enterococcus faecalis dissemination.
  • To identify mechanisms by which E. faecalis spreads systemically from the gut.

Main Methods:

  • Used mouse models to deplete colonic phagocytes and track bacterial dissemination.
  • Analyzed the role of specific macrophage receptors (CX3CR1, CCR7) in bacterial spread.
  • Assessed the impact of bacterial intracellular survival on dissemination.

Main Results:

  • Depletion of colonic phagocytes reduced E. faecalis spread to mesenteric lymph nodes.
  • Monocyte-derived macrophages expressing CX3CR1, but not CCR7, facilitated bacterial dissemination.
  • E. faecalis mutants with impaired intracellular survival showed reduced systemic spread.

Conclusions:

  • Colonic macrophages and their migration pathways are key to E. faecalis dissemination.
  • E. faecalis exploits host immune cell trafficking for systemic spread.
  • Modulating macrophage migration alongside antibiotics could prevent or treat opportunistic enteric infections.
Keywords:
CCR2CX3CR1Enterococcus faecaliscoloncommensaldisseminationgut-associated lymphoid tissuemacrophagesmigrationpathobiont

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